PROJECT 1: FRAILTY AND COMORBIDITY AS CAUSE AND CONSEQUENCE OF AGING ABSTRACT A fundamental gap exists in the translation of data from inbred animals in highly controlled laboratory environments to the experience of aging among genetically diverse humans living in complex environments. Companion dogs offer the unique opportunity to examine aging in a cohort that has differing genetic and environmental backgrounds, diseases that are individually diagnosed and treated, and extensive documentation of the medical progression through aging and causes of death. The overarching goal of this U19 Research Program is to understand the genetic and environmental determinants of healthy aging in companion dogs. As a critical step in achieving this goal, this Project aims to 1) define and standardize component measurements for three new axes of canine aging based on comorbidity, frailty and chronic inflammation using measurements translated from human populations that are feasible for measurement in a veterinary general practice; and 2) identify relationships among these three new aspects, and canine survival and healthy aging. To accomplish these goals, a full cohort of 10,000 companion dogs (the Longitudinal Study Population), their owners and veterinarians will be recruited to collect data on the dogs' health including demographics, medical history, basic physical measures and recorded diagnoses from veterinary medical records, as well as human lifestyle and dog care from owner questionnaires. A subset of dogs will be used to develop and test new procedures for assessing physical parameters, including gait speed and stair climbing, as well as non-standard measurements for body condition and obesity. Additional data will be collected on a select sample of 800 dogs (the Precision Cohort) to include an annual physical examination (body weight and size, body condition score, temperature, pulse, respiration), laboratory assays (CBC, biochemical profile and urine analysis), inflammatory status, and cognitive and mobility measurements needed to evaluate the three new phenotypic axes. Analyses will be conducted to test associations between developed exposure variables and survival including pathway outcomes such as frailty. This Project is critical to the overall mission of the Program, and will work in close synergy with Core D and all other Projects to test hypotheses regarding how healthy aging is influenced by the environment (Core D), genes (Project 2), molecular biomarkers and pathways (Project 3), and rapamycin treatment (Project 4). This Project has the potential not only to provide better methods to assist veterinarians and owners in keeping dogs healthy, but also to identify unique features of dog longevity and functionality that will be of the greatest value in translation to human populations.